Primary hepatocellular carcinoma (HCC) is a widespread cancer throughout the world, especially prevalent where the incidence of chronic hepatitis B (HBV) and hepatitis C (HCV) viral infections are endemic (Groen, (1999) Semin. Oncol. Nurs. 15, 48-57; Idilman et al., (1998) J. Viral. Hepat. 5, 110-117; Di Bisceglie et al., (1998) Hepatol. 28, 1161-1165; Johnson, (1997) Hepatogastroenerology 44, 307-312; Sheu, (1997) J. Gastroeneterol. Hepatol. 12, S309-313). Hepatocellular carcinomas are very malignant tumors that generally offer a poor prognosis, dependent on the size of the tumor, the effect on normal liver functions, and the involvement of metastases. They are best treated by surgical resection, when the tumors are diagnosed at a stage where this is a viable possibility, but the recurrence rate for these cancers remains high (Johnson, (1997) Hepatogastroenterology 44, 307-312; Schafer & Sorrell, (1999) Lancet 353, 1253-1257; Groen, (1999) Semin. Oncol. Nurs. 15, 48-57; Sitzman, (1995) World. J. Surg. 19, 790-794; DiCarlo, (1995) Hepato-Gastroenterol. 42, 222-259; Tanaka et al., (1996) Hepato-Gastroenterol. 43, 1172-1181; El-Assal et al., (1997) Surgery 122, 571-577).
Numerous risk factors for the development of HCC have been identified: cirrhosis, HBV or HCV infection, being male, alcohol-related liver disease, exposure to aflatoxins, vinyl chloride and radioactive thorium dioxide, cigarette smoking, ingestion of inorganic arsenic, the use of oral contraceptives and anabolic steroids, iron accumulation, and various inherited metabolic disorders (hemochromatosis, glycogen storage disease, porphyria, tyrosinemia, α-1-antitrypsin deficiency) (Di Bisceglie et al., (1998) Hepatol. 28, 1161-1165; Chen et al., (1997) J. Gastroenterol. Hepatol. 12, S294-308; Schafer & Sorrell (1999) Lancet 353, 1253-1257; Groen, (1999) Semin. Oncol. Nurs. 15, 48-57; Idilman et al., (1998) J. Viral. Hepat. 5, 110-117; Johnson, (1997) Hepato-Gastroenterol. 44, 307-312).
In addition to liver tumors attributed to hepatocellular carcinoma, there are liver tumors that arise as metastases from primary tumors in other parts of the body. These tumors most often metastasize from the gastrointestinal organs, primarily the colon and rectum, but it is possible for metastatic liver cancers to occur from primary cancers throughout the body (Sitzman 1990, Groen 1999). These cancers can be treated using the routine therapies such as chemotherapy, radiotherapy, surgical resection, liver transplantation, chemoembolization, cryosurgery, or a combination of therapies (Sitzman, (1990) Hepatic Neoplasia, in Bayless (editor) Current Therapy in Gastroenterology and Liver Disease, Marcel Dekker; Groen, (1999) Semin. Oncol. Nurs. 15, 48-57).
The characterization of genes that are differentially expressed in tumorigenesis is an important step in identifying those that are intimately involved in the details of a cell's transformation from normal to cancerous. Studies examining the gene expression of metastatic liver tumors and hepatocellular carcinomas in comparison with a set of normal liver tissues would produce data identifying genes that are not expressed in normal livers but have been switched on in tumors, as well as genes that have been completely turned off in these tumors during the progression from a normal to a malignant state. Such studies would also lead to the identification of genes that are expressed in tumor tissue at differing levels, but not expressed at any level in normal liver tissue. The identification of genes and ESTs that are expressed in both types of tumors, i.e., primary hepatocellular carcinomas as well as metastatic tumors of a different origin, and not in normal liver cells would be extremely valuable for the diagnosis of liver cancer.